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Almotriptan

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Almotriptan
Ball-and-stick model of the almotriptan molecule
Clinical data
Trade namesAxert, Almogran
Other namesLAS-31416; LAS31416
AHFS/Drugs.comMonograph
MedlinePlusa603028
License data
Routes of
administration		By mouth
Drug classSerotonin 5-HT1B, 5-HT1D, and 5-HT1F receptor agonist; Triptan; Antimigraine agent
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability70%
Protein binding35%
MetabolismLiver
Elimination half-life3–4 hours
Identifiers
  • N,N-dimethyl-2- [5-(pyrrolidin-1-ylsulfonylmethyl)- 1H-indol-3-yl]-ethanamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H25N3O2S
Molar mass335.47 g·mol−1
3D model (JSmol)
  • CN(C)CCc2c[nH]c3ccc(CS(=O)(=O)N1CCCC1)cc23
  • InChI=1S/C17H25N3O2S/c1-19(2)10-7-15-12-18-17-6-5-14(11-16(15)17)13-23(21,22)20-8-3-4-9-20/h5-6,11-12,18H,3-4,7-10,13H2,1-2H3 checkY
  • Key:WKEMJKQOLOHJLZ-UHFFFAOYSA-N checkY
  (verify)

Almotriptan, sold under the brand names Axert and Almogran among others, is a triptan medication used in the treatment of heavy migraine headache.[4][5][6][7]

Almotriptan was patented in 1992 and approved for medical use in 2000.[8] It was discovered and developed by Almirall-Prodesfarma.[7]

Medical uses

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Almotriptan is prescribed to treat the acute headache phase of migraine attacks with or without aura.[9] Almotriptan is approved in the US for the treatment of migraine in adolescent from 12 to 17 years of age.[10]

Effectiveness

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The efficacy and tolerability of almotriptan has been studied in numerous randomized, controlled trials totaling more than 4,800 adults with either moderate or severe attacks of migraine. Its efficacy is significantly more effective than placebo and alleviates nausea, photophobia and phonophobia linked to migraine attacks. Almotriptan has similar efficacy as a standard dose of sumatriptan, another triptan drug, and fewer adverse effects.[11]

Contraindications

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As with other triptans, almotriptan should not be used in patients with a history, symptoms or signs of ischaemic heart disease (myocardial infarction, angina pectoris, documented silent ischaemia, Prinzmetal's angina) or severe hypertension and uncontrolled mild or moderate hypertension. Other contraindications are previous cerebrovascular accident (CVA) or transient ischaemic attack (TIA), peripheral vascular disease, severe hepatic impairment, concomitant administration of ergotamine, ergotamine derivatives (including methysergide) and other 5-HT1B/D agonists.

Side effects

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Almotriptan has proved to have an adverse effects profile similar to placebo when used following the Summary of Product Characteristics instructions (see references).

Interactions

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Almotriptan is metabolized mainly by monoamine oxidase A (MAO-A) and to lesser extent by CYP3A4 and CYP2D6. Studies of drugs used as preventive against migraine (propranolol and verapamil), antidepressants (moclobemide and fluoxetine) yielded results that showed significant altering of the pharmacokinetics of almotriptan though they were deemed not clinically relevant.[11]

Pharmacology

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Mechanism of action

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Further information: Serotonin receptor agonist and Triptan § Mechanism of action
Almotriptan activities
Target Affinity (Ki, nM)
5-HT1A 186–850 (Ki)
3,310–>10,000 (EC50Tooltip half-maximal effective concentration)
5-HT1B 3.5–63 (Ki)
14–100 (EC50)
5-HT1D 5.5–16 (Ki)
18–20 (EC50)
5-HT1E >10,000 (Ki)
>10,000 (EC50)
5-HT1F 23 (Ki)
16–126 (EC50)
5-HT2A >10,000 (Ki)
>10,000 (EC50)
5-HT2B >10,000 (Ki)
6,310 (EC50)
5-HT2C ND (Ki)
ND (EC50)
5-HT3 ND
5-HT4 ND
5-HT5A ND
5-HT6 ND
5-HT7 347 (Ki)
>10,000 (EC50)
α >1,000
α1A–α1D ND
α2A–α2C ND
β >1,000
β1–β3 ND
D1, D2 >1,000
D3–D5 ND
H1 ND
H2 >1,000
H3, H4 ND
M1–M5 ND
I1, I2 ND
σ1, σ2 ND
TAAR1Tooltip Trace amine-associated receptor 1 ND
SERTTooltip Serotonin transporter ND
NETTooltip Norepinephrine transporter ND
DATTooltip Dopamine transporter ND
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [12][5][6][13][14][15][16]
[4][17][18][19][20][21][22]

Like all triptans, almotriptan has a high and specific affinity for serotonin 5-HT1B/1D receptors. Binding of the drug to the receptor leads to vasoconstriction of the cranial (brain) blood vessels and thus affects the redistribution of blood flow. Almotriptan significantly increases cerebral blood flow and reduces blood flow through extracerebral cranial vessels. Even though it affects cranial blood vessels a single standard dose of almotriptan has no clinically significant effect on blood pressure or heart rate in both young and elderly healthy volunteers. Larger doses seem to slightly increase blood pressure but not beyond clinical relevance.[11]

Pharmacokinetics

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Almotriptan has linear pharmacokinetics up to the 16-fold standard dose. Its biological half-life is 3 hours, and its bioavailability 70%.

Cmax is observed 1.5–4 hours after oral administration, and approximately 50% of the drug is excreted unchanged in the urine. Metabolism is mediated through the enzymes MAO-A and CYP3A4 and CYP2D6 oxidation.

Almotriptan clearance is moderately reduced in the elderly but does not require dose adjustment. Sex does not alter the pharmacokinetics of the drug. People with moderate-to-severe renal dysfunction are recommended to use only half the dose.[23]

Chemistry

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Almotriptan is a tryptamine derivative and a 5-substituted derivative of the psychedelic drug dimethyltryptamine (DMT).[24]

Its experimental and predicted log P are both 1.6.[24]

History

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Almotriptan was patented in 1992 and was approved for medical use in 2000.[8]

Society and culture

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Brand names

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Brand names include Axert (US, Canada), Almogran (Belgium, Denmark, Finland, France, Germany, Italy, Ireland Portugal, Spain, the United Kingdom, the Netherlands, Sweden, Switzerland, South Korea...), Almotrex (Italy), Almozen (Bulgaria and Poland), Dezamigren (Poland), and Amignul (Spain).

References

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  1. ^ "Almotriptan tablet, film coated". DailyMed. Retrieved 17 February 2021.
  2. ^ "Axert- almotriptan malate tablet, coated". DailyMed. Retrieved 17 February 2021.
  3. ^ "Active substance: almotriptan" (PDF). List of nationally authorised medicinal products. Europeans Medicines Agency. 11 February 2021.
  4. ^ a b Rabasseda X (January 2001). "Almotriptan in the treatment of migraine". Drugs Today (Barc). 37 (1): 5–21. doi:10.1358/dot.2001.37.1.844180. PMID 12783094.
  5. ^ a b Palacios, J.M., Rabasseda, X., Castaner, J. (1999). "Almotriptan". Drugs of the Future. 24 (4): 0367. doi:10.1358/dof.1999.024.04.482252. Retrieved 28 July 2025. Almotriptan is a selective 5-HT1B/1D receptor agonist which shows high and specific affinity for 5-HT1B/1D receptors in cranial vessels, but poor affinity for receptors in peripheral arteries. Affinity for 5-HT1A and 5-HT7 receptors was 35-51 times lower than for 5-HT1B/1D receptors, while affinity for most nonserotonergic receptors was negligible (Ki >1 µM) (6).
  6. ^ a b Holm KJ, Spencer CM (1999). "Almotriptan:". CNS Drugs. 11 (2): 159–164. doi:10.2165/00023210-199911020-00006. ISSN 1172-7047. Retrieved 28 July 2025. Receptor Binding: Almotriptan has equipotent and selective affinity for 5-HT1B and 5-HT1D receptors.[5] The drug shows a 35- to 51-fold higher affinity for 5-HT1B/1D receptors than other serotonin receptor subtypes (5- HT1A and 5-HT7). It has negligible affinity [inhibition constant (Ki ) >1000 nmol/L] for most relevant receptors that are not specific for serotonin, including the histamine H2 receptor, α-adrenoceptor, βadrenoceptor and dopamine D1 and D2 receptors.[6]
  7. ^ a b "Almotriptan". AdisInsight. 5 November 2023. Retrieved 28 July 2025.
  8. ^ a b Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 531. ISBN 9783527607495.
  9. ^ "Almotriptan Facts and Comparisons". Drugs.com. Retrieved 7 October 2012.
  10. ^ Gelfand AA, Goadsby PJ (October 2012). "Treatment of pediatric migraine in the emergency room". Pediatric Neurology. 47 (4). Elsevier BV: 233–241. doi:10.1016/j.pediatrneurol.2012.06.001. PMC 3681416. PMID 22964436.
  11. ^ a b c Keam SJ, Goa KL, Figgitt DP (2002). "Almotriptan: a review of its use in migraine". Drugs. 62 (2): 387–414. doi:10.2165/00003495-200262020-00010. PMID 11817980. S2CID 242752549.
  12. ^ Bou, J., Domenech, T., Gras, J., Beleta, J., Llenas, J., Fernandez, A. G., & Palacios, J. M. (1997). Pharmacological profile of almotriptan, a novel antimigraine agent. Cephalalgia, 17(3), 421-422. https://scholar.google.com/scholar?cluster=1949029248990535503
  13. ^ De Vries P, Villalón CM, Saxena PR (1999). "Pharmacology of triptans". Emerging Drugs. 4 (1): 107–125. doi:10.1517/14728214.4.1.107. ISSN 1361-9195.
  14. ^ Tfelt-Hansen P, De Vries P, Saxena PR (December 2000). "Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy". Drugs. 60 (6): 1259–1287. doi:10.2165/00003495-200060060-00003. PMID 11152011.
  15. ^ Deleu D, Hanssens Y (July 2000). "Current and emerging second-generation triptans in acute migraine therapy: a comparative review". J Clin Pharmacol. 40 (7): 687–700. doi:10.1177/00912700022009431. PMID 10883409.
  16. ^ Saxena PR, Tfelt-Hansen P (2001). "Success and failure of triptans". The Journal of Headache and Pain. 2 (1): 3–11. doi:10.1007/s101940170040. ISSN 1129-2369. PMC 3611827.
  17. ^ van den Brink M (22 December 1999). "Coronary Side Effects of Antimigraine Drugs From Patient to Receptor". RePub, Erasmus University Repository. Retrieved 19 June 2025. Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]
  18. ^ van den Broek RW (13 March 2002). "Vascular Effects of Antimigraine Drugs: pharmacology of human in vitro models in migraine". RePub, Erasmus University Repository. Retrieved 19 June 2025. Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]
  19. ^ Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJ, Zanelli E, et al. (December 2019). "Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan". British Journal of Pharmacology. 176 (24): 4681–4695. doi:10.1111/bph.14832. PMC 6965684. PMID 31418454. TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]
  20. ^ Reuter U, Neeb L (2012). "Lasmiditan hydrochloride". Drugs of the Future. 37 (10): 709. doi:10.1358/dof.2012.037.010.1873629. ISSN 0377-8282. Retrieved 19 June 2025.
  21. ^ Mitsikostas DD, Ward TN (2024). "Evidence-based symptomatic treatment of migraine". Migraine Management. Handbook of Clinical Neurology. Vol. 199. pp. 203–218. doi:10.1016/B978-0-12-823357-3.00004-5. ISBN 978-0-12-823357-3. PMID 38307647.
  22. ^ Comer MB (April 2002). "Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan". Headache. 42 (Suppl 2): S47 – S53. doi:10.1046/j.1526-4610.42.s2.2.x. PMID 12028320.
  23. ^ McEnroe JD, Fleishaker JC (2005). "Clinical pharmacokinetics of almotriptan, a serotonin 5-HT(1B/1D) receptor agonist for the treatment of migraine". Clinical Pharmacokinetics. 44 (3): 237–246. doi:10.2165/00003088-200544030-00002. PMID 15762767. S2CID 23136754.
  24. ^ a b "Almotriptan". PubChem. Retrieved 29 July 2025.
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